A high sensitive mass biosensor using a piezoresistive hole-type microcantilever has been developed. To optimize the cantilever shape for high sensitivity easily, we demonstrate frame-type cantilevers with holes on the surface fabricated by Focused Ion Beam (FIB) method and evaluate their sensitivity in both air and liquid. Resonance frequency of hole-type cantilevers increased about 20% and 40% in air and in water, respectively. On the other hand, while Q value decreased from 10% to 30% in air, it increased sharply from 0% to 50% in water with increasing of hole-size. Especially, when we increased the frame size from 0.5 mu m to 2.5 mu m, resonance frequency changing and Q value changing in water were 60% and 125%, respectively. However, the Q value of large hole (36x60 mu m(2)) in water inversely decreased due to the decline in rigidity. The sensitivity of hole-type cantilever of Delta m/Delta f (hole-size = 12x12 mu m(2); frame-size = 2.5 mu m) was 23.1 fg/Hz, 10 times smaller than the conventional type cantilever.